Abstract

Objective To compare the efficacy of etanercept (ETN) and methotrexate (MTX) versus MTX monotherapy for remission induction in patients
with early inflammatory arthritis.

Methods In a 78-week multicentre randomised placebo-controlled superiority trial, 110 DMARD-naïve patients with early clinical synovitis
(≥1 tender and swollen joint, and within 3 months of diagnosis) and either rheumatoid factor, anticitrullinated protein antibodies
or shared epitope positive were randomised 1:1 to receive MTX+ETN or MTX+placebo (PBO) for 52 weeks. Injections (ETN or PBO)
were stopped in all patients at week 52. In those with no tender or swollen joints (NTSJ) for >26 weeks, injections were stopped
early. If patients had NTSJ >12 weeks after stopping the injections, MTX was weaned. The primary endpoint was NTSJ at week
52.

Results No statistically significant difference was seen for the primary endpoint (NTSJ at week 52 (32.5% vs 28.1% [adjusted OR 1.32
(0.56 to 3.09), p=0.522]) in the MTX+ETN and MTX+PBO groups, respectively). The secondary endpoints did not differ between
groups at week 52 or 78. Exploratory analyses showed a higher proportions of patients with DAS28-CRP<2.6 in the MTX+ETN group
at week 2 (38.5% vs 9.2%, adjusted OR 8.87 (2.53 to 31.17), p=0.001) and week 12 (65.1% vs 43.8%, adjusted OR 2.49 (1.12 to
5.54), p=0.026).

Conclusions In this group of patients with early inflammatory arthritis, almost a third had no tender, swollen joints after 1 year. MTX+ETN
was not superior to MTX monotherapy in achieving this outcome. Clinical responses, however, including DAS28-CRP<2.6, were
achieved earlier with MTX+ETN combination therapy.

Trial registration number The EMPIRE trial is registered on the following trial registries: Eudract-2005-005467-29; ISRCTN 55428162 (http://www.controlled-trials.com/ISRCTN55428162/EMPIRE). The full trial protocol can be obtained from the corresponding author.